The aim of this program project is to continue to study the interaction of reovirus and its individual components with the nervous system. In addition, we will begin to extend these studies using poliovirus. Reovirus has been chosen because it is one of the best understood viruses in terms of understanding the function of several of the viral genes in viral host interactions. The program project will extend this knowledge base by continuing our studies with reovirus involving primary injury to muscle, spread of virus to the central nervous system (CNS) by blood or neural transport, trans-synaptic spread, spread within the CNS, characterization of the reovirus T3 receptor and identification of the reovirus T1 receptor. In addition, the cloning and expression of several reovirus genes will provide insights into the function of reovirus genes separate from their role in complex particles. Studies with polioviruses will be initiated utilizing the approaches shown to be fruitful ones for the reoviruses. Extensive collaboration will be carried out between the five participating investigators as well as a number of collaborators. The studies involve the following interdisciplinary areas: viral genetics and molecular biology, neuropathology, developmental neurobiology, and neuroimmunology.